Efficacy and Safety of Nivolumab Plus Ipilimumab vs Nivolumab Alone for Treatment of Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck : The Phase 2 CheckMate 714 Randomized Clinical Trial

Abstract

This randomized clinical trial investigates whether first-line treatment with nivolumab plus ipilimumab vs nivolumab alone improves objective response rate in adult patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).

Key Points

Question

Does first-line nivolumab plus ipilimumab provide clinical benefit vs nivolumab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN)?

Findings

In this randomized clinical trial of 425 adults with platinum-refractory or platinum-eligible R/M SCCHN, the primary end point of objective response rate benefit with nivolumab plus ipilimumab vs nivolumab was not met; results were generally similar in the population with platinum-eligible disease. Nivolumab plus ipilimumab had a manageable safety profile.

Meaning

In this trial, nivolumab plus ipilimumab had no clinical benefit over nivolumab alone as first-line treatment for R/M SCCHN.

Abstract

Importance

There remains an unmet need to improve clinical outcomes in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).

Objective

To evaluate clinical benefit of first-line nivolumab plus ipilimumab vs nivolumab alone in patients with R/M SCCHN.

Design, Setting, and Participants

The CheckMate 714, double-blind, phase 2 randomized clinical trial was conducted at 83 sites in 21 countries between October 20, 2016, and January 23, 2019. Eligible participants were aged 18 years or older and had platinum-refractory or platinum-eligible R/M SCCHN and no prior systemic therapy for R/M disease. Data were analyzed from October 20, 2016 (first patient, first visit), to March 8, 2019 (primary database lock), and April 6, 2020 (overall survival database lock).

Interventions

Patients were randomized 2:1 to receive nivolumab (3 mg/kg intravenously [IV] every 2 weeks) plus ipilimumab (1 mg/kg IV every 6 weeks) or nivolumab (3 mg/kg IV every 2 weeks) plus placebo for up to 2 years or until disease progression, unacceptable toxic effects, or consent withdrawal.

Main Outcomes and Measures

The primary end points were objective response rate (ORR) and duration of response between treatment arms by blinded independent central review in the population with platinum-refractory R/M SCCHN. Exploratory end points included safety.

Results

Of 425 included patients, 241 (56.7%; median age, 59 [range, 24-82] years; 194 males [80.5%]) had platinum-refractory disease (nivolumab plus ipilimumab, n = 159; nivolumab, n = 82) and 184 (43.3%; median age, 62 [range, 33-88] years; 152 males [82.6%]) had platinum-eligible disease (nivolumab plus ipilimumab, n = 123; nivolumab, n = 61). At primary database lock, the ORR in the population with platinum-refractory disease was 13.2% (95% CI, 8.4%-19.5%) with nivolumab plus ipilimumab vs 18.3% (95% CI, 10.6%-28.4%) with nivolumab (odds ratio [OR], 0.68; 95.5% CI, 0.33-1.43; P = .29). Median duration of response for nivolumab plus ipilimumab was not reached (NR) (95% CI, 11.0 months to NR) vs 11.1 months (95% CI, 4.1 months to NR) for nivolumab. In the population with platinum-eligible disease, the ORR was 20.3% (95% CI, 13.6%-28.5%) with nivolumab plus ipilimumab vs 29.5% (95% CI, 18.5%-42.6%) with nivolumab. The rates of grade 3 or 4 treatment-related adverse events with nivolumab plus ipilimumab vs nivolumab were 15.8% (25 of 158) vs 14.6% (12 of 82) in the population with platinum-refractory disease and 24.6% (30 of 122) vs 13.1% (8 of 61) in the population with platinum-eligible disease.

Conclusions and Relevance

The CheckMate 714 randomized clinical trial did not meet its primary end point of ORR benefit with first-line nivolumab plus ipilimumab vs nivolumab alone in platinum-refractory R/M SCCHN. Nivolumab plus ipilimumab was associated with an acceptable safety profile. Research to identify patient subpopulations in R/M SCCHN that would benefit from nivolumab plus ipilimumab over nivolumab monotherapy is warranted.

Trial Registration

ClinicalTrials.gov Identifier: NCT02823574